The functional biology of human milk oligosaccharides

doi:10.1016/j.earlhumdev.2015.09.001

Early Human Development

Volume 91, Issue 11, November 2015, Pages 619-622

https://doi.org/10.1016/j.earlhumdev.2015.09.001 Get rights and content

Abstract

Human milk oligosaccharides (HMOs) are a group of complex sugars that are highly abundant in human milk, but currently not present in infant formula. More than a hundred different HMOs have been identified so far. The amount and composition of HMOs are highly variable between women, and each structurally defined HMO might have a distinct functionality. HMOs are not digested by the infant and serve as metabolic substrates for select microbes, contributing to shape the infant gut microbiome. HMOs act as soluble decoy receptors that block the attachment of viral, bacterial or protozoan parasite pathogens to epithelial cell surface sugars, which may help prevent infectious diseases in the gut and also the respiratory and urinary tracts. HMOs are also antimicrobials that act as bacteriostatic or bacteriocidal agents. In addition, HMOs alter host epithelial and immune cell responses with potential benefits for the neonate. The article reviews current knowledge as well as future challenges and opportunities related to the functional biology of HMOs.

Section snippets

What are human milk oligosaccharides?

Human milk oligosaccharides (HMOs) are unconjugated complex glycans (sugars and carbohydrates) that are highly abundant in human milk, but not in infant formula [1]. One liter of mature human milk contains 10–15 g HMO, which often exceeds the total amount of protein and is 100- to 1000-fold higher than the concentration of oligosaccharides in bovine milk, which is the basis of most infant formula. Concentrations are even higher in human colostrum.

HMOs consist of five monosaccharide building

HMO metabolism

Once ingested by the breast-fed infant, HMOs resist the low stomach pH as well as degradation by the infant's pancreatic and brush border enzymes [6], [7]. Approximately, 1% of the ingested HMOs are absorbed, reach the infant's systemic circulation, and are excreted intact in the infant's urine [8], [9], [10]. The majority of HMOs are either metabolized by the infant's gut microbes or excreted intact with the infant's feces [11], [12].

Since HMOs are absorbed and appear in the systemic

HMOs are human milk prebiotics

According to a definition by Roberfroid et al., “a prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microbiota, that confers benefits upon host well-being and health” [13]. HMOs serve as metabolic substrates for specific bacteria like Bifidobacterium longum subsp. infantis. As a consequence, these bacteria have a growth advantage and thrive. Other bacteria that cannot utilize HMOs have a disadvantage

HMOs serve as antiadhesives

While the primary focus of HMO research has traditionally been on their prebiotic effects, HMOs are more than just “food for bugs”. Many viral, bacterial or protozoan parasite pathogens need to attach to epithelial cell surfaces to proliferate and in some cases invade and cause disease. Often, the initial attachment is to epithelial cell surface sugars (glycans) also known as the glycocalyx. While these glycans are conjugated to proteins or lipids, HMOs resemble some of the glycan structures

HMOs act as antimicrobials

HMOs may protect the neonate from pathogens by acting as prebiotics that provide beneficial bacteria with a growth advantage and by serving as antiadhesives at the interface of microbe–host interactions. In addition, HMOs may have a more direct way of keeping pathogens in check. We have recently shown that Streptococcus agalacticae (Group B Streptococcus; GBS) is no longer able to proliferate when HMOs are present (Lin et al., manuscript in preparation). GBS is one of the leading neonatal

HMOs alter epithelial and immune cell responses

HMOs may not only impact microbes directly, but also indirectly by altering host cell responses. HMOs have been shown to modulate intestinal epithelial cell apoptosis, proliferation and differentiation [33]. HMOs have also been shown to alter intestinal epithelial cell gene expression leading to changes in the cell surface glycocalyx [34]. Thus, HMOs may not only affect microbe–host attachment by serving as soluble decoy receptors as described above, but also by changing the expression of the

Conclusion

In conclusion, human milk, unlike the milk of most other mammals, contains very high concentrations of a structurally diverse group of more than a hundred different complex sugars called human milk oligosaccharides (HMOs). HMO composition follows a basic blueprint, but each woman produces a distinct profile of different HMOs at different concentrations that can change over the course of lactation. These inter- and intra-individual differences in HMO composition are in part determined by

Conflict of interest statement

The author has no conflicts of interest to declare. The author's research is funded in part by the National Institutes of Health (R00DK078668, R01AI104916, R21AI082434, R21HD080682, R03HD059717), and by research grants from Abbott Nutrition.

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The functional biology of human milk oligosaccharides

Abstract

Section snippets

What are human milk oligosaccharides?

HMO metabolism

HMOs are human milk prebiotics

HMOs serve as antiadhesives

HMOs act as antimicrobials

HMOs alter epithelial and immune cell responses

Conclusion

Conflict of interest statement

J Nutr

Am J Clin Nutr

Carbohydr Res

J Nutr

J Biol Chem

J Biol Chem

Obstet Gynecol

J Nutr

Human milk oligosaccharides: every baby needs a sugar mama

Glycobiology

Biochemical evidence that secretor gene, Se, is a structural gene encoding a specific fucosyltransferase

Proc Natl Acad Sci U. S. A.

Purification of the Lewis blood-group gene associated α-3/4-fucosyltransferase from human milk: an enzyme transferring fucose primarily to Type 1 and lactose-based oligosaccharide chains

Glycoconj J

Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation

Glycobiology

Detection of four human milk groups with respect to Lewis-blood-group-dependent oligosaccharides by serologic and chromatographic analysis

Adv Exp Med Biol

Incorporation of orally applied (13)C-galactose into milk lactose and oligosaccharides

Glycobiology

Urinary excretion of in vivo 13C-labelled milk oligosaccharides in breastfed infants

Br J Nutr

Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula

Acta Paediatr

CE-LIF-MSn profiling of oligosaccharides in human milk and feces of breast-fed babies

Electrophoresis

Glycoprofiling of bifidobacterial consumption of human milk oligosaccharides demonstrates strain specific, preferential consumption of small chain glycans secreted in early human lactation

J Agric Food Chem

Urinary excretion of in vivo ¹³C-labelled milk oligosaccharides in breastfed infants